The patient is a 15-year-old white male who was diagnosed with autism spectrum disorder at age 7 years. His mother says that although he met his early developmental milestones mostly on time, he did not start speaking until age 3 years and still did not use the words “I” and “me” appropriately. He did not join kindergarten classmates in play, preferring to play by himself with particular toys, specifically those with rolling parts such as trains and cars; his mother was not able to draw his attention to other toys.
He tended to have violent tantrums that included biting and hitting when his toys or play was encroached upon. Shortly after his autism spectrum disorder (ASD) was diagnosed, he was started on risperidone (one of only two medications approved by the Food and Drug Administration for use in autism) and responded very well to it. His speech improved and he was able to remain in mainstream school classrooms and form a few close friendships, although he still preferred to remain at home with his parents. He continued psychopharmacologic therapy for his ASD as he entered his teenage years.
During his last visit, the patient complained of fatigue. He was unkempt and had marked increases in ASD symptoms, especially poorer eye contact and increased perseveration. When asked about his emotional state he became confused and unsure, admitting that he did sometimes feel sad and angry but was not exactly sure why. He complained about people not understanding him or misinterpreting his behaviors. Although the youth gave no evidence of suicidal ideation or hopelessness, this history also may have been limited by his ASD.
His mother reported that the previous week he had gotten very angry and started to scream, yell, and cry when she moved his books while cleaning. In addition, she mentioned that he was not talking or eating as much as usual, and that his daily routines took longer. After further probing, the mother reported that these symptoms had recently increased in intensity but had started emerging a few months prior. She believed that his behavior was an indication of ASD symptoms and requested an increase in his risperidone.
Autism Spectrum Disorder with Comorbid Depression
Upon listening to both the patient’s self-reports and the mother’s observations, it became clear that he was suffering from comorbid depression. As a high-functioning patient with ASD, the patient was able to form close relationships; however, as he grew into adolescence he became more aware of the differences between him and his classmates. As he came to recognize his inabilities, he became unable to cope with the reality of his disorder and sank into a depression. There was no evidence of anxiety disorders, thyroid disease, or unreported changes in personal life.
Although the patient was not able to describe feeling depressed, many of the behaviors reported by him and his mother suggested the presence of a depressive disorder (see Sidebar). These behaviors were both specific to his ASD, including increased perseveration and more standard symptoms of depression such as diminished sleep and appetite.
How to Approach ASD-Affected Patients with Nonspecific Depressive Symptoms
- Investigate if there is marked change in behavior from both the patient and the caregiver(s).
- Determine triggers: recent stressful event, environmental stress, psychological trauma, significant life change, family history, etc.
- Note risk factors for depression in ASD: good insight and self-awareness, unsuccessful friendship attempts, social marginalization, etc.
- Evaluate changes in self-injurious behavior, compulsiveness, agitation, aggression, irritability, somatic complaints, or labile moods.
- Note decreases in self-care, adaptive functioning, and interest in preoccupations or regression of skills.
- Discuss the available treatment options with the patient and the caregiver(s), including risks and benefits of all treatments.
ASD = autism spectrum disorder.
Puberty and the increased self-awareness that it brings can trigger the onset of depressive symptoms.1 The challenge of comorbid ASD and depression is ascertaining the symptomatology of each disease. In a patient with ASD, depression frequently presents as an increase of existent ASD symptoms. What is important to note is not the symptoms themselves, but their heightened intensity. Moreover, patients with ASD are often unable to express their emotional states, and caregivers, teachers, and psychiatrists must rely upon observation.2 Because it is very easy to overlook depressive symptoms in patients with ASD, clinicians must make an added effort to explore such symptoms and inform the caregivers of the need for vigilance during periods of high stress, especially during adolescence, when depression is most common.3
In addition, there are other warning signs that put patients with ASD at a high risk of comorbid depression. Research shows a higher rate of depression in families of patients with ASD and comorbid depression.4 Moreover, those patients with high-functioning ASD and higher IQs are often able to recognize their own condition, and the pressures of perceived inadequacy can trigger depression.5
Treatment of depression with comorbid ASD can be difficult, and there is no consensus on the most efficacious course of action. For example, although the use of selective serotonin reuptake inhibitors (SSRIs) is the most obvious and effective means of treating depression comorbid with ASD, some studies have shown little to no improvement with SSRI use in patients with ASD, and SSRIs have a high incidence of side effects.
Studies have shown that patients with ASD and depression who take SSRIs have a greater risk of akathisia, disinhibition, or manic-like symptoms,1 Many studies have shown that the possibility of side effects is greatly increased in children with ASD, creating an even greater reason for concern when prescribing to that population.6 SSRI use is an option to be explored on a case-by-case basis.
Although tricyclic antidepressants have been utilized in the treatment of ASD patients with comorbid anxiety and depression, conflicting evidence of effect and side effect profiles require further research; they should not be considered as a first-line treatment.7
It is therefore incumbent on the prescribing physician to inform the patient and caregivers of the increased possibility of side effects and the vast unknowns about the efficacy of SSRIs on patients with ASD and comorbid depression. In an attempt to minimize the chance of side effects, a slower titration process is recommended; give the patient at least 4 to 6 weeks on low doses of the chosen medication to allow them to build tolerance to the side effects.
Talk therapy and cognitive-behavioral therapy, instead of medication or in conjunction with it, are two other options for treating depression comorbid with ASD.2
The patient stayed on a low dose of fluoxetine for 6 weeks and experienced no side effects. After the completion of the 6-week tolerance trial, his dosage was increased and he responded very well. He reports feeling “like himself again” and his mother confirms his return to his normal habits. He still complains about his social inabilities but is learning to both understand and express his emotions in talk therapy and is able to appreciate what progress he does make.
- Boyd K, Woodbury-Smith M, Szatmari P. Managing anxiety and depressive symptoms in adults with autism-spectrum disorders. J Psychiatry Neurosci. 2011;36(4):E35–36. doi:10.1503/jpn.110040 [CrossRef]
- Stewart ME, Barnard L, Pearson J, Hasan R, O’Brien G. Presentation of depression in autism and Asperger syndrome: a review. Autism. 2006;10(1):103–116. doi:10.1177/1362361306062013 [CrossRef]
- McPheeters ML, Davis A, Navarre JR 2nd, Scott TA. Family report of ASD concomitant with depression or anxiety among US children. J Autism Dev Disord. 2011;41(5):646–653. doi:10.1007/s10803-010-1085-9 [CrossRef]
- Mazefsky CA, Conner CM, Oswald DP. Association between depression and anxiety in high-functioning children with autism spectrum disorders and maternal mood symptoms. Autism Res. 2010;3(3):120–7. doi:10.1002/aur.133 [CrossRef]
- Magnuson KM, Constantino JN. Characterization of depression children with autism spectrum disorders. J Dev Behav Pediatr. 2011Apr15. [Epub ahead of print]. doi:10.1097/DBP.0b013e318213f56c [CrossRef]
- Williams K, Wheeler DM, Silove N, Hazell P. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2010;(8):CD004677.
- Hurwitz R, Blackmore R, Hazell P, Williams K, Woolfenden S. Tricyclic antidepressants for autism spectrum disorders (ASD) in children and adolescents. Cochrane Database Syst Rev.2012;3:CD008372.